Medial prefrontal cortex oxytocin-opioid receptors interaction in spatial memory processing in rats.

Medial prefrontal cortex (mPFC), a forebrain structure, is involved in many brain functions such as learning and memory. In the present study, the effect of intra-mPFC microinjection of oxytocin, atosiban, morphine and naloxone was investigated on memory processing. Two guide cannulas were implanted into the right and left sides of the mPFC in ketamine and xylazine-anesthetized rats. To assess spatial memory function MWM test was performed by four training sessions of four trials. On day 5, a probe test was conducted after drugs microinjection. Significant differences were observed in learning activities during training days before microinjection of drugs. Intra-mPFC microinjections of oxytocin (5 and 10 ng/site) significantly increased memory related activities. This effect of oxytocin was inhibited by prior microinjection of atosiban (20 ng/site). On the other hand, morphine microinjection at doses of 5 and 10 μg/site into the mPFC significantly decreased memory related activities that were prevented by prior administration of naloxone (5 μg/site) and oxytocin (5 and 10 ng/site). In addition, intra-mPFC combined microinjections of low doses of oxytocin (2.5 ng/site) and naloxone (1 μg/site) improved memory function. By increasing the doses of oxytocin (5 ng/site) and naloxone (5 μg/site), a more documented improving effect was observed. These results showed that memory performance was impaired by activation of mPFC opioid receptors in rats. In addition, oxytocin in the mPFC improved memory function and prevented memory impairment-induced by morphine. Moreover, an interaction between oxytocin and opioid systems was also appeared in the present study.